Huperzia

Traditionally, plants are a rich source of AChE inhibitors. People from the Caucasus used bulbs of snowdrops Galanthus sp.) to treat forgetfulness [25]. The active compound in this plant has been isolated and called galanthamine. Other plant-derived AChE inhibitors used for treatment of Alzheimer s disease include Huperzine A from Huperzia serrata and Rivastigmine (Excelon). The latter is a derivative from physostigmine isolated from the calabar bean, Physos-tigma vmmosum. 

Lycopodium complanatum Lycopodium cemuum Huperzia serrata... 

Gao, W Li, Y Jiang, S. and Zhu, D. 2000. Three lycopodium alkaloid A-oxides from Huperzia serrata. Planta Medica, 66 664-667. 

Huperzia serrata (Thunb.) Trev. [= Lycopodium serratum Thunb.], Lycopodiophyta from China... 

A Papua New Guinea sponge, Pseudoceratina sp., contains the unusual alkaloids ceratamines A (1142) and B (1143), and a biogenesis involving histidine and tyrosine is proposed (1173). The fermentation broth from Aspergillus fischeri var. thermomutatus has yielded CJ-12662 (1144) and UK-88051 (1145) (1174). The former metabolite was confirmed by X-ray spectroscopy and partial synthesis. A marine-derived Streptomyces sp. produces the novel pyrrolizidine 5-chlorobohem-amine C (1146), which was shown not to be an isolation artifact (1175). The Chinese medicinal plant Huperzia serrata has furnished 2-chlorohyperzine E (1147) (1176). 

Wanibuchi K, Zhang P, Abe T, Morita H, Kohno T, Qien G, Noguchi H (2007) An acridone-producing novel multifunctional type III polyketide synthase from Huperzia serrata. FEBS J 274 1073-1082... 

Huperzia serrata (moss), Lycopodium selago (fir club moss) — not to be confused with non-toxic L. clanatum... 

TABLE 4-1. HA Detected by Thin-Layer Chromatography in Whole Plant Extract of Huperzia and Related Genera... 

Ma, X. Q. Jiang, S. H. Zhu, D. Y. Alkaloid patterns in huperzia and some related genera of Lycopodiaceae Sensu Lato occuring in China and their contribution to classification. Biochem. Syst. EcoL, 1998, 26 723-727. 

Acetate is also a precursor of several groups of alkaloids in the form of a polyketide chain that interacts with an unknown nitrogen source (as in the terpene alkaloids). Examples of acetate-derived alkaloids are coniine—the toxic principle of Conium maculatum, pinidine—from several Pinus species, and the naphthy-lisoquinoline alkaloids (e.g., ancistrocladine)—showing antimalarial and anti-HIV activity. The latter alkaloids are apparently derived from the oxidative coupling of two pentaketide units. Huperzine A, currently in clinical trials for the treatment of Alzheimer s disease and isolated from the club moss (Serrata huperzia), is derived from a polyacetate precursor (Fig. 46). 

The family of Lycopodiaceae contains three genera of clubmoss, Huperzia, Lycopodium, and Lycopodiella. 

The impact of Traditional Chinese Medicine on modern western drugs is demonstrated not only by commercialized therapeutic agents such as camptothecin or artemisinin but also by clinical candidates like huperzine A, an acetylcholinesterase inhibitor to treat Alzheimer s disease [103]. Huperzine A can be isolated from both, Huperzia serrata, and H. selago [104,105]. Because huperzine A is produced only at very low levels a synthetic approach has been developed in order to provide sufficient quantities for preclinical toxicology studies and clinical trials. 

Eburnamenine Eburnamine Eburnamonine Geissoschizol Huperzia serrata Huperzine A Hypericum perforatum St. John s Wort Hyperoside... 

Huperzine A, isolated from the Chinese herb Huperzia serrata (Thunb) Trev, is a novel reversible and selective AChE inhibitor. ZT-1 is a novel analog of huperzine A. ZT-1 is a prodrug that is rapidly absorbed and converted into huperzine A, and ZT-1 is well tolerated in healthy Chinese volunteers [173],... 

A myriad of natural compounds have been tested for the past 20 years in a frenetic search for agents with potential effects against AD neuropathology. Some of these compounds include alkaloids from the calabar bean (Physostigma venenosum) huperzine A from Huperzia serrata-, galantamine from the snowdrop Galanthus woronowii cannabinoids (cannabidiol from Cannabis sativa) ... 

More recently, Ben-Hameda et al. (57) used this combination to improve the sensitivity of the determination of Huperzine A (a natural product from Huperzia serrata used to treat Alzheimer s disease and incorporated as a food supplement). BGE concentration (acetate buffer pH = 4.6) and voltage were used as input parameters, while peak area, peak height, or migration time were individually studied as outputs. In each case, optimal ANN architecture was (2 3 1). To maximize the sensitivity, relatively high concentrations of the BGE and low voltages were required (optimum conditions were 50mM sodium acetate and 10kV). 

Huperzine A, a potent anticholinesterase alkaloid, and huperzine B were separated from a Chinese medicinal herb, Huperzia serrata (Thunb) Trev. Lycopodium serratum Thunb.), (Lycopodiaceae), by Liu et al [25]. The plant was used in Zhejiang Province of China for treatment of some mental disorders. 

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